Contributions of the amygdala and medial prefrontal cortex to incentive cue responding

Abstract

Reward-seeking behavior is controlled by neuronal circuits that include the basolateral nucleus of amygdala (BLA), medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and ventral tegmental area. Using a discriminative stimulus (DS) task in which an intermittently presented cue (DS) directs the animals to make an operant response for sucrose, we previously demonstrated that dopamine receptor antagonism in the NAc reduced reinforced cue responding, whereas general inactivation of the NAc increased behavioral responding in the absence of the cue. Because they send major glutamatergic projections to the NAc, the BLA and mPFC may also contribute to reward-seeking behaviors modulated by the NAc. In this study we compare the effects of BLA and mPFC inactivation on the performance of a DS task. BLA inactivation by combined GABA A and GABA B agonists impaired cue responding with minimal effects on operant behavior in the absence of cues. Dorsal mPFC (dmPFC) inactivation also inhibited cue-evoked reward-seeking. In contrast, ventral mPFC (vmPFC) inactivation disinhibited responding to unrewarded cues with less influence on reinforced cue responding. These findings demonstrate that the BLA and dmPFC facilitate cue-evoked rewardseeking, whereas, in the same task the vmPFC exerts inhibitory control over unrewarded behaviors.Keywords basolateral nucleus; infralimbic cortex; nucleus accumbens; prelimbic cortex; cingulate cortex; reward-seeking behavior Cue-evoked reward-seeking behaviors require recognition of learned cues that predict reward availability and selection of appropriate motor responses. Performance of reward-seeking behavior requires integrated functions of multiple brain areas including the basolateral nucleus of the amygdala (BLA), medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and ventral tegmental area (VTA). The BLA and mPFC play crucial roles in reward-related © 2008 IBRO. Published by Elsevier Ltd. All rights reserved.Corresponding author: Akinori Ishikawa 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan Phone: 81-836-22-2211 Fax: 81-836-22-2211.jp. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 July 9. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript behaviors and are major sources of glutamatergic afferents to the NAc (McGeorge and Faull, 1989;Brog et al., 1993;Zahm, 2000). The NAc, which receives excitatory inputs from the BLA and mPFC and projects via both direct and indir...

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

“…For example, activity is increased in IL neurons following cue-and context-induced cocaine and heroin seeking, and IL inactivation diminishes reinstatement of extinguished cocaine, methamphetamine, and heroin seeking (7). Furthermore, PL inactivation increases spontaneous and premature behaviors (8)(9)(10) and impairs response inhibition (11). Together, these results imply that neuronal networks within PL and IL can contribute to both response execution and inhibition.…”

“…PL inactivation during discriminative stimulus (DS)-driven reward-seeking reduces cue-driven behaviors (8). However, PL inactivation also increases nonspecific (8) and premature lever responding (9,10), and PL is important in inhibiting responses during a stop-signal reaction time task (11).…”

“…PL inactivation during discriminative stimulus (DS)-driven reward-seeking reduces cue-driven behaviors (8). However, PL inactivation also increases nonspecific (8) and premature lever responding (9,10), and PL is important in inhibiting responses during a stop-signal reaction time task (11). IL inactivation during DS task performance increases responses generally, including those triggered by a nonrewarded stimulus (NS) (8), increases premature responding on five-choice serial reaction time tasks (12), and increases spontaneous recovery and reinstatement (13).…”

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

“…As the neural circuits that include the nucleus accumbens, amygdala, and prefrontal cortex are known to have crucial roles in emotions, motivation, and reward (Cardinal et al, 2002;Carlezon and Thomas, 2009;Ishikawa et al, 2008;Kalivas and Nakamura, 1999), we examined the effects of encounter stimulation on c-Fos expression in these brain regions. Encounter stimulation increased c-Fos expression in the nucleus accumbens shell of group-and isolationreared mice to a similar degree.…”

Integrating Optogenetic and Pharmacological Approaches to Study Neural Circuit Function: Current Applications and Future Directions

“…Two recent studies that used projection-specific targeting to study amygdala function highlight how activity in one brain region may mediate distinct behavioral responses depending on the strength and pattern of activity that it communicates to specific downstream targets Tye et al, 2011). The amygdala is a critical structure for processing negative emotions, such a fear (Fanselow and Gale, 2003;Pare et al, 2004;Ehrlich et al, 2009;LeDoux, 2012), but also plays an integral role in the encoding and behavioral responses to salient environmental cues of both negative and positive valence (Paton et al, 2006;Ambroggi et al, 2008;Ishikawa et al, 2008;Tye et al, 2008;Shabel and Janak, 2009;Gardner, 2011). Pathway-specific optogenetic modulation of the glutamatergic projection from the BLA to the nucleus accumbens (NAc), including the activation and inactivation of BLA terminals in the NAc, confirmed that this circuitry is both necessary and sufficient for cue-driven motivated behavior .…”